The ventilatory rate determines the PCO2. Increased ventilation decreases PCO2, whereas decreased ventilation increases it (Fig. 37.8 ). The blood PCO2 and pH are important regulators of the ventilatory rate. Chemoreceptors located in the brainstem (ventral surface of the medulla) and periphery (carotid and aortic bodies) sense changes in PCO2 and [H+] and alter the ventilatory rate appropriately. Thus when metabolic acidosis occurs, a rise in the [H+] (decrease in pH) stimulates the ventilatory rate. Conversely, during metabolic alkalosis, a decreased [H+] (increase in pH) reduces the ventilatory rate. With maximal hyperventilation, the PCO2 can be reduced to approximately •Fig. 37.8 EffectofventilatoryrateonalveolarPCO2andthusarterialbloodPCO2.
10 mm Hg. Because hypoxia, a potent stimulator of ventilation, also develops with hypoventilation, the degree to which the PCO2 can be increased is limited. In an otherwise normal individual, hypoventilation cannot raise the PCO2 above 60 mm Hg. The respiratory response to metabolic acid-base disturbances may be initiated within minutes but may require several hours to complete.
The third and final line of defense against acid-base disorders involves the kidneys. In response to an alteration in plasma pH and PCO2, the kidneys make appropriate adjustments in the excretion of RNAE. The renal response may require several days to reach completion because it takes hours to days to increase the synthesis and activity of the proximal tubule enzymes involved in NH4 + production. In the case of acidosis (increased [H+] or PCO2), the secretion of H+ by the nephron is stimulated and the entire filtered load of HCO3 − is reabsorbed. Titratable acid excretion is increased and production and excretion of NH4 + is also stimulated, and thus RNAE is increased (
Fig. 37.9). The new HCO3 − generated during the process of net acid excretion is added to the body, and the plasma [HCO3 −] increases.
When metabolic alkalosis exists (decreased [H+]), the filtered load of HCO3 − is increased (plasma [HCO3 −] is elevated). With respiratory alkalosis (decreased PCO2), plasma [HCO3 −] is decreased and thus the filtered load is decreased. In both conditions, secretion of H+ by the nephron is inhibited. As a result, HCO3 − excretion is increased. At the same time, excretion of both titratable acid and NH4 + is decreased. Thus RNAE is decreased and HCO3 − appears in urine. Also, some HCO3 − is secreted into urine by the HCO3 −-secreting intercalated cells of the distal tubule and collecting duct. With enhanced excretion of HCO3 − , plasma [HCO3 −] decreases.
•Fig. 37.9 Responseofthenephrontoacidosis.Pi,phosphate;PTH,parathyroidhormone;Rhbg&Rhcg,rhesusglycoproteins;RNAE,renalnetacidexcretion;TA,titratableacid;V,urineflowrate.